[chasil]

The only two architectural questions that I know of were...

The weak memory model:

https://devblogs.microsoft.com/oldnewthing/20170817-00/?p=96...

Inability to address low-power designs:

https://en.m.wikipedia.org/wiki/StrongARM

"According to Allen Baum, the StrongARM traces its history to attempts to make a low-power version of the DEC Alpha, which DEC's engineers quickly concluded was not possible."

The other major problem with the Alpha was the high license costs of DEC operating systems, which greatly helped put it in the grave.

[masklinn]

And incapable of working with unaligned values or values smaller than 4 bytes. Weren’t there also cache coherence issues?

Alpha kinda had you finish the hardware in software.